Dysregulation of piwi‐interacting RNA expression in primary human cardiac myocytes during early phase of Trypanosoma cruzi infection

Abstract

Trypanosoma cruzi, the causative agent of Chagas Disease, is an obligate intracellular parasite that has caused severe mortality and morbidity historically in Central and South America. Due to international travel, globalization, and migration, this neglected tropical disease is now present in most industrialized countries. About 30% of those who develop chronic T. cruzi infection will exhibit various pathologies, including cardiomyopathies, neurological and/or gastrointestinal diseases. We and others have implicated gene dysregulation as necessary in facilitating T. cruzi infection. However, the role of small noncoding RNAs during infection is still being investigated. Hence, the molecular mechanisms that contribute to chronic chagas cardiomyopathies remains to be elucidated. In this study, we aim to delineate dysregulation of a class of small non-coding RNAs, piwi-interacting RNAs (piRNAs), during the early phase of T. cruzi infection in primary human cardiomyocytes (PHCM). We hypothesize that dysregulated piRNAs target genes that may play important roles in infection. After parasite challenge, we extracted PHCM RNA for subsequent RNA sequencing. We then utilized bioinformatic tools in order to analyze differential expression of piRNAs, to predict mRNA targeting, and to map piRNAs to biological pathways. We found an average of 21,595,866 of clean reads (88.4%) mapped to the human reference genome. During the course of infection, T. cruzi induced differential expression of 217 unique piRNAs. In silico analysis predicted that both dysregulated known and novel piRNAs could target several genes of interest, including NFATC2, FOS, and TGF-b1, and related genes known to interact with these targets. These novel findings are the first to implicate that Trypanosoma cruzi induces differential expression of piRNAs in PHCM, which advances our knowledge of piRNAs in infectious disease pathogenesis.